Protection of macaques against a SHIV with a homologous HIV-1 Env and a pathogenic SHIV-89.6P with a heterologous Env by vaccination with multiple gene-deleted SHIVs

To evaluate the potential of SHIVs as anti-HIV-1 live vaccines, we construc ted two gene-deleted SHIVs, designated SHIV-drn and SHIV-dxrn. The former l acks vpr/nef and the latter lacks vpx/vpr/nef. Four macaques that had been vaccinated with SHIV-drn were challenged with SHIV-NM-3rN, which has an HIV -1 Env that is the same as that of SHIV-drn, No challenge virus was detecte d by DNA PCR in, or recovered from, two of the macaques, In the other two, challenge virus was detected once and twice, respectively. Plasma viral loa ds were much lower than those in unvaccinated controls. Another four macaqu es were vaccinated with SHIV-dxrn. These macaques showed resistance but les s than that of SHIV-drn-vaccinated macaques. When the two SHIV-drn-vaccinat ed macaques were challenged with pathogenic SHIV-89.6P, which has an HIV-1 Env that is antigenically different from that of SHIV-drn, replication of t he challenge virus was restricted, and the usual decrease in the number of CD4(+) cells was prevented. In this protection, it is noteworthy that prote ction involved not only neutralizing antibodies and killer cell activity, b ut also other unknown specific and nonspecific immunity elicited by the inf ection. (C) 1999 Academic Press.